Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes

Abstract

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Rare evolution of CSF3R-mutated chronic neutrophilic leukemia to t(4;12)(q12;p13) acute myeloid leukemia with SETBP1 mutation

“…To the best of our knowledge, we have described, for the first time, a unique episode of transformation to AML with t(4;12)(q12;p13) in a patient previously diagnosed as CNL. The t(4;12)(q12;p13) translocation is a very rare rearrangement, reported in less than 1% of AML or myelodysplastic syndrome cases and mainly occurring in de novo AML [3] . To date, only 7 patients have been described in the blast phase of myeloproliferative neoplasm [ 3 , 4 ].…”

“…The t(4;12)(q12;p13) translocation is a very rare rearrangement, reported in less than 1% of AML or myelodysplastic syndrome cases and mainly occurring in de novo AML [3] . To date, only 7 patients have been described in the blast phase of myeloproliferative neoplasm [ 3 , 4 ]. In our case, several previously described features of t(4;12)(q12;p13), such as CD7 expression, absence of myeloperoxidase activity, unique blast morphology with multilineage dysplasia and failure of the first induction chemotherapy were present [ 3 , 4 ].…”

“…In the t(4;12)(q12;p13) translocation, ETV6 for 12p13 has been reported to be variably fused to a genomic region which frequently involves CHIC2 and PDGFRA for 4q12 [3] . However, the impact of the CHIC2 or PDGFRA/ETV6 fusion protein on AML pathogenesis is not well understood.…”

“…Intriguingly, the additional molecular events that have recently been reported in patients with t(4;12)(q12;p13)-positive AML are in line with those found in CNL. The most commonly mutated genes in the t(4;12)(q12;p13) AML were ASXL1 (50%) and SRSF2 (31%), but SETBP1 and CBL were also mutated in 6% of the cases [3] . The ASXL1, SRSF2, SETBP1 and CBL mutations are found in 30–81%, 21–44%, 14–56% and 25% of patients with CNL, respectively [1] .…”